Clinicopathology profile evaluated against several risk factors in breast cancer cases
VoL
8, No 2, April - June 1999
Clinicopathology and risk factors in breast cancer 123
Clinicopathology profTle evaluated against several risk factors
in breast cancer cases
Idral Darwis*, Muchlis Ramli*, Didid Tjindarbumi*, Esti Soetrisno#,Gunawan Tjahjadi#, Endang Sri
Roostini#, Santoso Cornain#, Drupadi S Dillon-, Joedo Prihartono$, Setyawati Budiningsihs, Goi Sakamoto'
Yoshiyuki Ohno', Kenji Wakair
Abstrak
Telah dilakt'tkan penelitian dua ratus dua puluh enam kasus kanker payudara (KPD) yang berhubungan dengan aspek klinik dan
patologi serta faktor risiko yang berhubungatt dengan terjadinya keganasan payudara. Distribusi terbanyak pada umur antara 35-55
tahun clengan frekuensi tertinggi antara umur 40-50 tahun. Tidak didapatkan perbednan lokasi tumor pada payudara kanan atau kiri
serta distribusi pre-menopause maupun post-menopause. Delapan puluh satu koma enarn persen KPD ditemukan pada stadium lanjut
(stacliutn IIIA: 17,77o, IIIB: 56,2Vo dan IV: I l,9Ea), sedangkan stadium I: I,3Vo dan stadium II: ll,97o. Tujuh puluh tima dari 226 kasus
dilakukan tindakan pembedalnn: 60Vo mastektomi simpel, 26,7Vo mastektomi radikaL dan l,3Vo: breast concerving treatment (BCT). Histopatol.ogi dari jaringan payudara dari 2I4 kasus clklapatkan karsinoma int,astf yang terdiri dari: 90,47o karsinoma eluktal invasif dan
9,6Vo tipe khusus. Dilakukan analisa dari beberapafaktor risiko seperti status kawin, umur pada saat kawin pertama, untur menarche,
sttttus menoPause, laktasi, riwayat keluarga KPD, penggunaan kontrasepsi dan konsumsi tinggi lemak. Hasil dari metode kasus kontol
ntenunjukkan bahwa faktor-faktor status menopause, laktasi dan konsumsi tinggi lemak meningkatkut risiko terjadinya KPD, dengan
risiko relatif ntasing-rnasing: 1,5 1, I,83 dan2,6l.
Abstract
The second batch case-controL study on breast cancer hcts been conducted as a joint study between Indonesian antl Japan. Two
hwrdrerl antl hventy six (226) cases of breast cancer was coLlected to assess the riskfactors ancl evaluatetl for their clinical presentation
of the clisease. The age distribution in some high risk areas showed at age 35 to 55 years, with a single peak between 40 to 50. There
was no dffirence in nuntber of cases in respect to tu,nor site anel menopausal status. The majority of cases 81.6 Vo were in advanced
stage (lllA: 17.7%, IIIB: 56.2Vo and IV: Il.9Vo) whiLe in contrast stage I and II were very rare (I.3Vo and ]l.9Vo respectively). OnLy 75
cases were operabLe; simple masîectomy was the most frequent sur7ery carried out (60.0Vo), followed by moclffied radical mastectomy
(26.7Vo), classical radical mastectomy ( 12Vo) ancl breast consenting treatnrcnt ( I .3Vo). The specimens were reviewecl using classification
reconntentletl by the Japanese Breast Cancer Society reveaLecl invasive ductaL carcinoma (90.4 Vo) and the special type (9.6 Vo). Several
riskfactors were analyzedfor their influence to the deveLopment of breast cance4 narnely: marital status, age atrtr$ marriage, menarche,
menoltattsaL status, lactation, fLtmily history of breas't canceq, use of contraceptive ancl fat consLuryttion. Among the characteristics studied,
tltefoLlowingfactorssignificantlyincreasedtheriskof breastca.ncer:menopausaLsturus(RR=1.51:95VoCI:1.10-2.09),non-lackLting
children(RR=1.83;95VoCI:1.07-3.11)arulfatconsuntption(RR=2.61;95VoCI:1.86-3.68),whiletheuseofcontraceptiveshoweclprotective effect. The fi,ndings wilL be discr.tssed in its benef.t relative to both the improvement of tlxe treament modality ancl the cancer control
P
roSranx.
Keywords: Breast cance6 clinicopathologicaL, case-controL study, epidemiology
INTRODUCTION
* Department
of Surgery, Facuhy of Medicine, University
Inelonesia, Jakarta I 04 30, I ndo nesia
# Deparment
*
*
.
t
Indones ia,
of
of Pathology, FctcuLty of Medicine, University
of
Jakarta I 04 30, Indonesia
Department of Nutitiort, FacuLty of Medicine, Liniversity of
Indonesia, J akarta I 0430, Indonesia
Department of Community Medicine, Faculty of Medicine,
University of Indonesia, Jakarta 10320, Indonesia
Department of Pathology, Cancer Institute Hospitctl, Tbkyo
170, Japan
Deparment of Prettenth,e Medicine, SchooL of Medicine,
Nagoya University, Nagoya 466, Japan
Carcinoma of the breast continue to baffle the surgeons and the pathologists for the unpredictable biological behavior and many gap in the knowledge of
the factors that either control or influence tumor
genesis and growth. In Indonesia breast cancer
ranked second most common malignant tumor of the
females. Up to 678 cases of breast cancer were hos-
pitalized in Dr. Cipto Mangunkusumo Hospital,
Jakarta, during the 5 years period-1986-1990. Data
collected from Pathological Base Cancer Registry
showed relative frequency l8.O3Vo with Age Stand-
Med J Inclones
Darwis et al
ardize Cancer Ratio (ASCAP.) 17.84Vo
18.44Vo (ASCAR I7.48Vo) in 1989.r
1988 and
More articles have been published on breast cancer'2'
7 but accumulation of knowledge has not produce any
commensurate degree
of agreement among
research
worker and clinicians on epidemiological, etiological,
pathological and treatment problem of breast cancer.
Thomas Huxley wrote "A great tragedy of science the staying of a beautiful hypothesis by an ugly fact".
Wider understanding of different modalities, natural
history of the disease and host-tumor relationship are
some of the encouraging factors toward better salvage of this disease. A team work is needed for the
management of breast cancer without prejudice to the
of breast cancer cases in women started and peaked
at comparatively younger age as compared to women
in the Western countries. Table 1 and Figurel shows
the details of age incidence and the commonest inci-
in age groups 30-39, 40-49 and 50-59
(28.3Vo, 30.1Vo and 28.8Vo) respectively. The incidence sharply decrease with advancing age. The
youngest case of breast cancer was 29 years old and
the oldest 74 years.
dence was
Thble
1. Distribution of 226 cases of breast cancer
and 552 con-
trols according to age of patients
Age
Cases
Control
%
Vo
25-29
J
1.3
4
0.9
30-39
40-49
64
28.3
t36
30. r
68
30.
l
141
31.2
This study was conducted to find out the clinico-
50-59
65
28.8
115
25.4
pathological findings and incidence of the disease in
relation to other parameters along with the known etiological factors.
60-69
>70
23
10,2
53
11.7
3
1.3
3
0;7
specialty.
552
226
Total
MATERIAL AND METHODS
Materials consisted of women who underwent treatment at the Division of Surgical Oncology, Department of Surgery - Dr. Cipto Mangunkusumo Hospital, Jakarta, during the period of February 7992 to
September 1995 and were diagnosed as having histologically confirmed breast carcinoma. The medical
records comprising 226 cases, aged 29 to 74 years
(median age 45 years), were reviewed. A detailed
clinical history and clinical examination were taken.
Clinical staging was done by criteria according to the
International UICC TNM System for Malignant Tumor8 and the surgical specimens were reviewed using
the classification recommended by the
Japanese
Breast Cancer Society (1984)e.
With the same cases (226) several potential factors
for breast carcinoma, namely: marital status, age at
first marriage, menarche, menopausal status, lactation, family history of breast cancer, use of contraceptive and fat consumption were recorded. A casecontrol study design with 1:2ratio was applied in this
assessment. Each risk factor was assessed through
univariate analysis and was measured its estimated
Relative Risk and 95Vo Confidence Intervals.
RESULTS
Age
We found that signif,rcant increase of the proportion
70
Figure 1, Age distribution of 226 cases of breast cancer
(histogram)
Menopausal status
Correlation with hormonal status is shown in Figure
2. One hundred thirteen (50.22Vo) cases were premenopausal and 172 (49.78Vo) were post menopausal.
Vol 8, No 2,
114
April - June
Clinicopathology ancl risk factors in breast cancer 125
1999
TFeatment
1:irit!1i1,3
The treatment modality in operable cases (33.2Vo) in
shown in Table 4. Radical mastectomy and modified
radical mastectomy were adopted as initial treatment
in the Department of Surgery for Stage I and Stage II
which was done in 29 cases. Adjuvant radiation was
performed if there was clinical evidence of regional
metastasis. Stage IIIA cases were treated by simple
mastectomy (60Vo).
110
106
Thble
4.
Type of operation performed in 75 cases
Type of operation
No. of
Radical mastectomy
100
Premeno
7o
9
l2.o
Modifi ed radical mastectomy
20
26.7
Simple mastectomy
45
60.0
I
1.3
Lumpectomy
Postmeno
cases
Figure 2, Distributiott of 225 breast cancer by menopausaL status
Clinical features
Histopathology
The right breast was involved in 48.2Vo,left breast in
48.'lVo and bilateral tumor was present in 1.87o (Table
2). Staging of the disease (Table 3) was done by rhe
UICC TNM Classification of Malignant Tumors criterta:, l.3Vo were in stage I, ll.9Vo in stage II, 17 .7Vo
in stage IIIA, 56.20/o in stage IIIB and 11.97a in stage
IV. The highest number of cases had advanced disease (Stage IIIB) and proposed treatment was pallia-
Histology classification of Japanese Breast Cancer
Society have been adopted to classify breast carcinoma (Table 5). Scirrhous adenocarcinoma was the
commonest type of cancer.
Table
tron.
Table
2.
5.
Histological pâttern of breast cancer cases according to
classification recommended by Japanese Breast Cancer
Society (1984)
Histological types
Side involvement of breast cancer cases
No. of cases
Right Left
Non-invasive carcinoma
Side affected
No. of cases
Vo
Right
109
48.2
Left
lr0
48.7
4
1.8
Bilateral
Invasive carcinoma
a. Invasive ductal carcinoma
al. Papillotubular
l5
7
8
a2. Solid-tubular
65
27
38
ll8
61
57
a3. Scirrhous
Thble
3.
Distribution ol'breast cancer cases according to clinical
staging (n = 226)
Stage
I
Cases
Va
1.3
II
27
I1.9
IIIA
40
17.7
IIIB
IV
t27
56.2
27
11.9
2
0.8
226
100.0
Total
bl.
Mucinous carcinoma
5
4
I
l0
5
5
b3. Invasive lobular carcinoma 5
b4. Squamous cell carcinoma
I
2
3
b2, Medullary
3
Unknown
b. Special types
carcinoma
c. Unclassified and other
ll
225
Notes:
four
cases bilateral
I
r06
1r3
%o
126
Table
Darwis et
6.
Metl J Indones
aL
Univariate logistic analySis of odds ratios (RR) and
confidence interval (CI) for breast cancer risk factors
Covariates
Cases Controls
Menarche
RR
t5
116
2t8
1.00
r.r3
lt2
270
1.00
113
r80
177
354
45
2
97
0
No
t'70
3r1
Yes
49
133
1L)4
418
28
No
213
Yes
6
Menopausal status
No
Yes
Marital status
Married
Widowed
Unmarried
Use of contraception
Lactation
Yes
No
957o Cl
Reference
(0.82-1.56)
Reference
1.5r
(1.r0-2.09)*
1.00
0.4
(0.62-t.40)
1.00
0.67
(0.46-0.98)*
Reference
Reference
J3
1.00
1.83
(1.07-3.il)'k
422
22
1.00
0.50
(0.22-1.3s)
121
222
222
1.00
0.81
(0.59-1.12)
1.00
2.61
Family BC
Reference
Retèrence
Age of marriage
)
20
< 20
yrs
yrs
98
Reference
Fat consumpt
26
65
232
l6l
220
I 15
258
ll1
r94
Reference
(
1
.86-3.68)*
Calories intake
<
>
1854
1854
1.00
t.28
Reference
(0.93-1.'7'1)
8, No 2, April - June 1999
Clinicopathology and risk factors in breast cancer 123
Clinicopathology profTle evaluated against several risk factors
in breast cancer cases
Idral Darwis*, Muchlis Ramli*, Didid Tjindarbumi*, Esti Soetrisno#,Gunawan Tjahjadi#, Endang Sri
Roostini#, Santoso Cornain#, Drupadi S Dillon-, Joedo Prihartono$, Setyawati Budiningsihs, Goi Sakamoto'
Yoshiyuki Ohno', Kenji Wakair
Abstrak
Telah dilakt'tkan penelitian dua ratus dua puluh enam kasus kanker payudara (KPD) yang berhubungan dengan aspek klinik dan
patologi serta faktor risiko yang berhubungatt dengan terjadinya keganasan payudara. Distribusi terbanyak pada umur antara 35-55
tahun clengan frekuensi tertinggi antara umur 40-50 tahun. Tidak didapatkan perbednan lokasi tumor pada payudara kanan atau kiri
serta distribusi pre-menopause maupun post-menopause. Delapan puluh satu koma enarn persen KPD ditemukan pada stadium lanjut
(stacliutn IIIA: 17,77o, IIIB: 56,2Vo dan IV: I l,9Ea), sedangkan stadium I: I,3Vo dan stadium II: ll,97o. Tujuh puluh tima dari 226 kasus
dilakukan tindakan pembedalnn: 60Vo mastektomi simpel, 26,7Vo mastektomi radikaL dan l,3Vo: breast concerving treatment (BCT). Histopatol.ogi dari jaringan payudara dari 2I4 kasus clklapatkan karsinoma int,astf yang terdiri dari: 90,47o karsinoma eluktal invasif dan
9,6Vo tipe khusus. Dilakukan analisa dari beberapafaktor risiko seperti status kawin, umur pada saat kawin pertama, untur menarche,
sttttus menoPause, laktasi, riwayat keluarga KPD, penggunaan kontrasepsi dan konsumsi tinggi lemak. Hasil dari metode kasus kontol
ntenunjukkan bahwa faktor-faktor status menopause, laktasi dan konsumsi tinggi lemak meningkatkut risiko terjadinya KPD, dengan
risiko relatif ntasing-rnasing: 1,5 1, I,83 dan2,6l.
Abstract
The second batch case-controL study on breast cancer hcts been conducted as a joint study between Indonesian antl Japan. Two
hwrdrerl antl hventy six (226) cases of breast cancer was coLlected to assess the riskfactors ancl evaluatetl for their clinical presentation
of the clisease. The age distribution in some high risk areas showed at age 35 to 55 years, with a single peak between 40 to 50. There
was no dffirence in nuntber of cases in respect to tu,nor site anel menopausal status. The majority of cases 81.6 Vo were in advanced
stage (lllA: 17.7%, IIIB: 56.2Vo and IV: Il.9Vo) whiLe in contrast stage I and II were very rare (I.3Vo and ]l.9Vo respectively). OnLy 75
cases were operabLe; simple masîectomy was the most frequent sur7ery carried out (60.0Vo), followed by moclffied radical mastectomy
(26.7Vo), classical radical mastectomy ( 12Vo) ancl breast consenting treatnrcnt ( I .3Vo). The specimens were reviewecl using classification
reconntentletl by the Japanese Breast Cancer Society reveaLecl invasive ductaL carcinoma (90.4 Vo) and the special type (9.6 Vo). Several
riskfactors were analyzedfor their influence to the deveLopment of breast cance4 narnely: marital status, age atrtr$ marriage, menarche,
menoltattsaL status, lactation, fLtmily history of breas't canceq, use of contraceptive ancl fat consLuryttion. Among the characteristics studied,
tltefoLlowingfactorssignificantlyincreasedtheriskof breastca.ncer:menopausaLsturus(RR=1.51:95VoCI:1.10-2.09),non-lackLting
children(RR=1.83;95VoCI:1.07-3.11)arulfatconsuntption(RR=2.61;95VoCI:1.86-3.68),whiletheuseofcontraceptiveshoweclprotective effect. The fi,ndings wilL be discr.tssed in its benef.t relative to both the improvement of tlxe treament modality ancl the cancer control
P
roSranx.
Keywords: Breast cance6 clinicopathologicaL, case-controL study, epidemiology
INTRODUCTION
* Department
of Surgery, Facuhy of Medicine, University
Inelonesia, Jakarta I 04 30, I ndo nesia
# Deparment
*
*
.
t
Indones ia,
of
of Pathology, FctcuLty of Medicine, University
of
Jakarta I 04 30, Indonesia
Department of Nutitiort, FacuLty of Medicine, Liniversity of
Indonesia, J akarta I 0430, Indonesia
Department of Community Medicine, Faculty of Medicine,
University of Indonesia, Jakarta 10320, Indonesia
Department of Pathology, Cancer Institute Hospitctl, Tbkyo
170, Japan
Deparment of Prettenth,e Medicine, SchooL of Medicine,
Nagoya University, Nagoya 466, Japan
Carcinoma of the breast continue to baffle the surgeons and the pathologists for the unpredictable biological behavior and many gap in the knowledge of
the factors that either control or influence tumor
genesis and growth. In Indonesia breast cancer
ranked second most common malignant tumor of the
females. Up to 678 cases of breast cancer were hos-
pitalized in Dr. Cipto Mangunkusumo Hospital,
Jakarta, during the 5 years period-1986-1990. Data
collected from Pathological Base Cancer Registry
showed relative frequency l8.O3Vo with Age Stand-
Med J Inclones
Darwis et al
ardize Cancer Ratio (ASCAP.) 17.84Vo
18.44Vo (ASCAR I7.48Vo) in 1989.r
1988 and
More articles have been published on breast cancer'2'
7 but accumulation of knowledge has not produce any
commensurate degree
of agreement among
research
worker and clinicians on epidemiological, etiological,
pathological and treatment problem of breast cancer.
Thomas Huxley wrote "A great tragedy of science the staying of a beautiful hypothesis by an ugly fact".
Wider understanding of different modalities, natural
history of the disease and host-tumor relationship are
some of the encouraging factors toward better salvage of this disease. A team work is needed for the
management of breast cancer without prejudice to the
of breast cancer cases in women started and peaked
at comparatively younger age as compared to women
in the Western countries. Table 1 and Figurel shows
the details of age incidence and the commonest inci-
in age groups 30-39, 40-49 and 50-59
(28.3Vo, 30.1Vo and 28.8Vo) respectively. The incidence sharply decrease with advancing age. The
youngest case of breast cancer was 29 years old and
the oldest 74 years.
dence was
Thble
1. Distribution of 226 cases of breast cancer
and 552 con-
trols according to age of patients
Age
Cases
Control
%
Vo
25-29
J
1.3
4
0.9
30-39
40-49
64
28.3
t36
30. r
68
30.
l
141
31.2
This study was conducted to find out the clinico-
50-59
65
28.8
115
25.4
pathological findings and incidence of the disease in
relation to other parameters along with the known etiological factors.
60-69
>70
23
10,2
53
11.7
3
1.3
3
0;7
specialty.
552
226
Total
MATERIAL AND METHODS
Materials consisted of women who underwent treatment at the Division of Surgical Oncology, Department of Surgery - Dr. Cipto Mangunkusumo Hospital, Jakarta, during the period of February 7992 to
September 1995 and were diagnosed as having histologically confirmed breast carcinoma. The medical
records comprising 226 cases, aged 29 to 74 years
(median age 45 years), were reviewed. A detailed
clinical history and clinical examination were taken.
Clinical staging was done by criteria according to the
International UICC TNM System for Malignant Tumor8 and the surgical specimens were reviewed using
the classification recommended by the
Japanese
Breast Cancer Society (1984)e.
With the same cases (226) several potential factors
for breast carcinoma, namely: marital status, age at
first marriage, menarche, menopausal status, lactation, family history of breast cancer, use of contraceptive and fat consumption were recorded. A casecontrol study design with 1:2ratio was applied in this
assessment. Each risk factor was assessed through
univariate analysis and was measured its estimated
Relative Risk and 95Vo Confidence Intervals.
RESULTS
Age
We found that signif,rcant increase of the proportion
70
Figure 1, Age distribution of 226 cases of breast cancer
(histogram)
Menopausal status
Correlation with hormonal status is shown in Figure
2. One hundred thirteen (50.22Vo) cases were premenopausal and 172 (49.78Vo) were post menopausal.
Vol 8, No 2,
114
April - June
Clinicopathology ancl risk factors in breast cancer 125
1999
TFeatment
1:irit!1i1,3
The treatment modality in operable cases (33.2Vo) in
shown in Table 4. Radical mastectomy and modified
radical mastectomy were adopted as initial treatment
in the Department of Surgery for Stage I and Stage II
which was done in 29 cases. Adjuvant radiation was
performed if there was clinical evidence of regional
metastasis. Stage IIIA cases were treated by simple
mastectomy (60Vo).
110
106
Thble
4.
Type of operation performed in 75 cases
Type of operation
No. of
Radical mastectomy
100
Premeno
7o
9
l2.o
Modifi ed radical mastectomy
20
26.7
Simple mastectomy
45
60.0
I
1.3
Lumpectomy
Postmeno
cases
Figure 2, Distributiott of 225 breast cancer by menopausaL status
Clinical features
Histopathology
The right breast was involved in 48.2Vo,left breast in
48.'lVo and bilateral tumor was present in 1.87o (Table
2). Staging of the disease (Table 3) was done by rhe
UICC TNM Classification of Malignant Tumors criterta:, l.3Vo were in stage I, ll.9Vo in stage II, 17 .7Vo
in stage IIIA, 56.20/o in stage IIIB and 11.97a in stage
IV. The highest number of cases had advanced disease (Stage IIIB) and proposed treatment was pallia-
Histology classification of Japanese Breast Cancer
Society have been adopted to classify breast carcinoma (Table 5). Scirrhous adenocarcinoma was the
commonest type of cancer.
Table
tron.
Table
2.
5.
Histological pâttern of breast cancer cases according to
classification recommended by Japanese Breast Cancer
Society (1984)
Histological types
Side involvement of breast cancer cases
No. of cases
Right Left
Non-invasive carcinoma
Side affected
No. of cases
Vo
Right
109
48.2
Left
lr0
48.7
4
1.8
Bilateral
Invasive carcinoma
a. Invasive ductal carcinoma
al. Papillotubular
l5
7
8
a2. Solid-tubular
65
27
38
ll8
61
57
a3. Scirrhous
Thble
3.
Distribution ol'breast cancer cases according to clinical
staging (n = 226)
Stage
I
Cases
Va
1.3
II
27
I1.9
IIIA
40
17.7
IIIB
IV
t27
56.2
27
11.9
2
0.8
226
100.0
Total
bl.
Mucinous carcinoma
5
4
I
l0
5
5
b3. Invasive lobular carcinoma 5
b4. Squamous cell carcinoma
I
2
3
b2, Medullary
3
Unknown
b. Special types
carcinoma
c. Unclassified and other
ll
225
Notes:
four
cases bilateral
I
r06
1r3
%o
126
Table
Darwis et
6.
Metl J Indones
aL
Univariate logistic analySis of odds ratios (RR) and
confidence interval (CI) for breast cancer risk factors
Covariates
Cases Controls
Menarche
RR
t5
116
2t8
1.00
r.r3
lt2
270
1.00
113
r80
177
354
45
2
97
0
No
t'70
3r1
Yes
49
133
1L)4
418
28
No
213
Yes
6
Menopausal status
No
Yes
Marital status
Married
Widowed
Unmarried
Use of contraception
Lactation
Yes
No
957o Cl
Reference
(0.82-1.56)
Reference
1.5r
(1.r0-2.09)*
1.00
0.4
(0.62-t.40)
1.00
0.67
(0.46-0.98)*
Reference
Reference
J3
1.00
1.83
(1.07-3.il)'k
422
22
1.00
0.50
(0.22-1.3s)
121
222
222
1.00
0.81
(0.59-1.12)
1.00
2.61
Family BC
Reference
Retèrence
Age of marriage
)
20
< 20
yrs
yrs
98
Reference
Fat consumpt
26
65
232
l6l
220
I 15
258
ll1
r94
Reference
(
1
.86-3.68)*
Calories intake
<
>
1854
1854
1.00
t.28
Reference
(0.93-1.'7'1)